HJURP Is a Cell-Cycle-Dependent Maintenance and Deposition Factor of CENP-A at Centromeres

被引:509
作者
Dunleavy, Elaine M. [1 ]
Roche, Daniele [1 ]
Tagami, Hideaki [2 ]
Lacoste, Nicolas [1 ]
Ray-Gallet, Dominique [1 ]
Nakamura, Yusuke [3 ]
Daigo, Yataro [3 ]
Nakatani, Yoshihiro [2 ]
Almouzni-Pettinotti, Genevieve [1 ]
机构
[1] Inst Curie, CNRS, Lab Nucl Dynam & Genome Plast, UMR218, F-75248 Paris 05, France
[2] Nagoya City Univ, Grad Sch Nat Sci, Mizuho Ku, Aichi 4678501, Japan
[3] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Mol Med Lab, Tokyo 1130033, Japan
关键词
HISTONE H3 VARIANT; FISSION YEAST SCM3; BUDDING YEAST; CHROMATIN; PROTEIN; KINETOCHORE; COMPLEX; NUCLEOSOME; CHAPERONE; DNA;
D O I
10.1016/j.cell.2009.02.040
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The histone H3 variant CenH3, called CENP-A in humans, is central in centromeric chromatin to ensure proper chromosome segregation. In the absence of an underlying DNA sequence, it is still unclear how CENP-A deposition at centromeres is determined. Here, we purified non-nucleosomal CENP-A complexes to identify direct CENP-A partners involved in such a mechanism and identified HJURP. HJURP was not detected in H3.1- or H3.3-containing complexes, indicating its specificity for CENP- A. HJURP centromeric localization is cell cycle regulated, and its transient appearance at the centromere coincides precisely with the proposed time window for new CENP- A deposition. Furthermore, HJURP downregulation leads to a major reduction in CENP-A at centromeres and impairs deposition of newly synthesized CENP-A, causing mitotic defects. We conclude that HJURP is a key factor for CENP-A deposition and maintenance at centromeres.
引用
收藏
页码:485 / 497
页数:13
相关论文
共 64 条
[1]   Centromeres are specialized replication domains in heterochromatin [J].
Ahmad, K ;
Henikoff, S .
JOURNAL OF CELL BIOLOGY, 2001, 153 (01) :101-109
[2]   Epigenetic regulation of centromeric chromatin: old dogs, new tricks? [J].
Allshire, Robin C. ;
Karpen, Gary H. .
NATURE REVIEWS GENETICS, 2008, 9 (12) :923-937
[3]   Neocentromeres: Role in human disease, evolution, and centromere study [J].
Amor, DJ ;
Choo, KHA .
AMERICAN JOURNAL OF HUMAN GENETICS, 2002, 71 (04) :695-714
[4]   The histone variant CENP-A and centromere specification [J].
Black, Ben E. ;
Bassett, Emily A. .
CURRENT OPINION IN CELL BIOLOGY, 2008, 20 (01) :91-100
[5]   Centromere identity maintained by nucleosomes assembled with histone H3 containing the CENP-A targeting domain [J].
Black, Ben E. ;
Jansen, Lars E. T. ;
Maddox, Paul S. ;
Foltz, Daniel R. ;
Desai, Arshad B. ;
Shah, Jagesh V. ;
Cleveland, Don W. .
MOLECULAR CELL, 2007, 25 (02) :309-322
[6]  
BLOWER MD, 2002, NAT REV MOL CELL BIO, V3, P575
[7]   Scm3 is essential to recruit the histone H3 variant Cse4 to centromeres and to maintain a functional kinetochore [J].
Camahort, Raymond ;
Li, Bing ;
Florens, Laurence ;
Swanson, Selene K. ;
Washburn, Michael P. ;
Gerton, Jennifer L. .
MOLECULAR CELL, 2007, 26 (06) :853-865
[8]   Simple centromere, complex kinetochore: linking spindle microtubules and centromeric DNA in budding yeast [J].
Cheeseman, IM ;
Drubin, DG ;
Barnes, G .
JOURNAL OF CELL BIOLOGY, 2002, 157 (02) :199-203
[9]   Centromeres and kinetochores: From epigenetics to mitotic checkpoint signaling [J].
Cleveland, DW ;
Mao, YH ;
Sullivan, KF .
CELL, 2003, 112 (04) :407-421
[10]   Proteolysis contributes to the exclusive centromere localization of the yeast Cse4/CENP-A histone H3 variant [J].
Collins, KA ;
Furuyama, S ;
Biggins, S .
CURRENT BIOLOGY, 2004, 14 (21) :1968-1972